A Study of Escalating Doses of Romidepsin in Association With CHOP in the Treatment of Peripheral T-Cell Lymphomas

Condition(s) targeted: Peripheral T Cell Lymphoma

Intervention: Romidepsin and CHOP (Drug); Romidepsin and CHOP (Drug); Romidepsin and CHOP (Drug); Romidepsin and CHOP (Drug)

Phase: Phase 1/Phase 2

Status: Recruiting

Sponsored by: The Lymphoma Academic Research Organisation

Official(s) and/or principal investigator(s):
Bertrand COIFFIER, Professor, Principal Investigator

Overall contact:
Sabine BALOUET, PM, Phone: +33(0)472669333, Email: sabine.balouet@gelarc.org

This study is an open label, multicenter study with two phases:

- A dose escalation phase of Romidepsin administered IV at day 1 and 8 or at day 1

without day 8 in combination with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP)administered every 3 weeks for 8 cycles in patients with T-cell lymphoma.

- An expansion phase in order to assess the safety and the efficacy of the association of

the recommended dose of Romidepsin associated with CHOP in a population of patients with T-cell lymphoma.

Official title: A Phase IB/II Study of Escalating Doses of Romidepsin (Istodax®) in Association With CHOP (Ro-CHOP) in the Treatment of Peripheral T-Cell Lymphomas

Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome: Incidence of Dose Limiting Toxicities

Secondary outcome:

Complete Response Rate(CR) at the end of treatment

Progression-free survival (PFS)

Duration of Response

Safety of association Romidepsin-CHOP

Overall Response at the end of treatment

Overall Survival (OS)

Detailed description: The primary objective of the study is to determine the feasibility of the combination and the recommended dose (RD) of Romidepsin when administered in association with CHOP in a population of patients with newly diagnosed Peripheral T-cell lymphoma (PTCL) as measured by the toxicities during treatment.

Secondary objectives:

- To assess the safety of the association Romidepsin and CHOP,

- To assess the efficacy of the association of Romidepsin and CHOP: response rate and

complete response rate, progression-free survival, response duration and overall survival.

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

Criteria:

1. Inclusion Criteria:

1. Patients with histologically confirmed Peripheral T-cell Lymphoma (PTCL), not previously treated ; all subtypes may be included except HTLV-1-related T-cell lymphoma, cutaneous T-cell lymphoma (mycosis fungoid and Sézary syndrome), and ALK+ PTCL,

2. Ann Arbor stages II - IV

3. Aged from 18 to 80 years,

4. ECOG performance status 0, 1 or 2,

5. Signed informed consent,

6. Negative pregnancy test for females of childbearing potential (FCBP),

7. FCBP using an effective method of birth control (i. e. hormonal contraceptive, intrauterine device, diaphragm with spermicide, condom with spermicide or abstinence) for the treatment period and for 1 month thereafter; Males using an effective method of birth control for the treatment period and 3 months thereafter,

8. Life expectancy of ≥ 90 days (3 months)

2. Exclusion Criteria:

1. Other types of lymphomas, e. g. B-cell lymphoma

2. Ann Arbor stage I

3. Previous treatment for PTCL with immunotherapy or chemotherapy except for short-term corticosteroids before inclusion

4. Previous radiotherapy for PTCL except if localized to one lymph node area

5. Central nervous system - meningeal involvement

6. Contraindication to any drug contained in the chemotherapy regimen

7. HIV infection, active hepatitis B or C

8. Any serious active disease or co-morbid medical condition (according to investigator's decision)

9. Any of the following laboratory abnormalities

- Absolute neutrophil count (ANC) < 1,500 cells/mm3 (1. 5 x 109/L),

- Platelet count < 100,000/mm3 (100 x 109/L), or 75,000 if bone marrow is

involved,

- Serum SGOT/AST or SGPT/ALT ≥ 5. 0 x upper limit of normal (ULN),

- Serum total bilirubin > 2. 0 mg/dL (34 µmol/L), except in case of hemolytic

anemia,

- Low K+ (inferior to low normal level) and low Mg+ (inferior to low normal

level)levels, except if corrected before beginning the chemotherapy,

10. Use of oral contraceptive and contraceptive patches,

11. Calculated creatinine clearance (Cockcroft-Gault formula) of < 50 mL /min,

12. Prior history of malignancies other than lymphoma (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless the subject has been free of the disease for ≥ 3 years,

13. Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form,

14. Left Ventricular Ejection Fraction < 45% (calculated by echocardiographic or scintigraphic methods),

15. Patients with congenital long QT syndrome, history of significant cardiovascular disease and/or taking drugs leading to significant QT prolongation,

16. Corrected QT interval > 480 msec (using the fridericia formula)

17. Use of any standard or experimental anti-cancer drug therapy within 28 days of the initiation (Day 1) of study drug ,

18. Pregnant or lactating females or women of childbearing potential not will-ing to use an adequate method of birth control for the duration of the study.

Sabine BALOUET, PM, Phone: +33(0)472669333, Email: sabine.balouet@gelarc.org

Hôpital Henri Mondor, Créteil 94010, France; Recruiting
Jehan DUPUIS, MD, Email: jehan.dupuis@hmn.aphp.fr
Jehan DUPUIS, MD, Principal Investigator

CHU de Dijon, Dijon 21000, France; Recruiting
Olivier CASASNOVAS, MD, Email: olivier.casasnovas@chu-dijon.fr
Olivier CASASNOVAS, MD, Principal Investigator

Hôpital Claude Huriez, Lille 59037, France; Recruiting
Franck MORSCHHAUSER, MD, Email: f-morschhauser@chru-lille.fr
Franck MORSCHHAUSER, MD, Principal Investigator

Centre Léon Bérard, Lyon cedex 8 69373, France; Recruiting
Hervé GHESQUIERES, MD, Email: GHESQUIE@lyon.fnclcc.fr
Hervé GHESQUIERES, MD, Principal Investigator

Hôpital St Louis, Paris 75475, France; Recruiting
Catherine THIEBLEMONT, Professor, Email: catherine.thieblemont@sls.ap-hop-paris.fr
Catherine THIEBLEMONT, Professor, Principal Investigator

Centre Hospitalier Lyon Sud, Pierre-Bénite 69495, France; Recruiting
Bertrand COIFFIER, Professor, Email: bertrand.coiffier@chu-lyon.fr
Bertrand COIFFIER, Professor, Principal Investigator

Centre Henri Becquerel, Rouen 76038, France; Recruiting
Hervé TILLY, Professor, Email: herve.tilly@rouen.fnclcc.fr
Hervé TILLY, Professor, Principal Investigator

Institut Gustave Roussy, Villejuif 94805, France; Recruiting
Vincent RIBRAG, MD, Email: vincent.ribrag@igr.fr
Vincent RIBRAG, MD, Principal Investigator

Starting date: January 2011
Last updated: October 8, 2012